The purpose of this study was to evaluate the effects of two alternative chemotherapy regimes on the quality of life (QoL) of patients with advanced breast cancer. In a multicentre trial, 283 patients were randomised to receive either docetaxel (T) or sequential methotrexate and 5-fluorouracil (MF). QoL was assessed at baseline and before each treatment using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30). Initial compliance in the QoL study was 96% and the overall compliance 82%. QoL data were available for 245 patients (T 130 and 115 MF). Both treatment groups showed some improvement in emotional functioning during treatment, with a significant difference favouring the MF group at treatment cycles 5 and 6. In the T group, the scores on the other functional scales remained stable throughout the first six cycles. There were significant differences favouring the MF group on the social functioning scale at treatment cycle 6 and on the Global QoL scale at treatment cycles 5 and 6. On most symptom and single-item scales there were no statistically significant differences between the groups. However, at baseline, the T patients reported more appetite loss, at treatment cycles 2-4, the MF patients reported more nausea/vomiting, and at treatment cycle 6, the T patients reported more symptoms of fatigue, dyspnoea and insomnia. There were no statistically significant differences between the groups in the mean change scores of the functional and symptom scales. Interindividual variance was, however, larger in the T group. Differences in QoL between the two treatment groups were minor. Hence, given the expectancy of comparable QoL outcomes, the choice of treatment should be made on the basis of the expected clinical effect.